Tolerance induction by intrathymic inoculation prevents chronic renal allograft rejection.
BACKGROUND
These experiments investigated the ability of the donor-specific unresponsiveness created by the intrathymic inoculation of donor alloantigen to effectively prevent chronic rejection in an established rat model of chronic renal allograft rejection.


METHODS
Three study groups were examined: (1) Allograft controls--F-344 rats received a Lewis renal allograft plus 10 days of low-dose cyclosporine (CsA); (2) isograft controls--F-344 rats received an F-344 renal isograft and low-dose CsA; (3) experimental group--F-344 rats received a T-cell depleted syngeneic bone marrow transplant and intrathymic injection of Lewis bone marrow. Twenty-one days after bone marrow transplant, these animals received a Lewis renal allograft.


RESULTS
Allograft controls demonstrated severe parenchymal fibrosis; isograft controls and intrathymic (IT) animals failed to develop this lesion. Immunohistochemical analysis revealed increased CD4+ T cells infiltrating the cortex of the allograft controls. Cytokine interferon-gamma and interleukin-2 transcripts were strongly positive in allograft controls and were absent from isograft controls and IT allografts as determined by reverse transcriptase-polymerase chain reaction. Analysis of tolerant grafts by flow microfluorimetry and genomic DNA amplification could not detect chimerism to a level of < 0.1%.


CONCLUSIONS
IT inoculation of donor alloantigen can confer long-term unresponsiveness and prevent the development of the characteristic lesions of chronic rejection.
Blom
D
D
Department of Surgery, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
Morrissey
N
N
Mesonero
C
C
Zuo
X J
XJ
Jordan
S
S
Fisher
T
T
Bronsther
O
O
Orloff
M S
MS
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006084:Graft Rejection / Q000517:prevention & control*; D007108:Immune Tolerance; D007267:Injections; D007519:Isoantigens / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008212:Lymphocyte Depletion; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013950:Thymus Gland; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
D007519:Isoantigens